CANRENONE AS A PARTIAL AGONIST AT THE DIGITALIS RECEPTOR-SITE OF SODIUM-POTASSIUM-ACTIVATED ADENOSINE-TRIPHOSPHATASE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 217  (3) , 784-790
Abstract
Carenone, a spironolactone metabolite, was tested for its possible effects on (Na+-K+) ATPase activity [Mg2+-dependent, (Na+-K+)-activated ATP phosphohydrolase (EC 3.6.1.3)] and ouabain interaction with the enzyme. Canrenone competitively antagonized the binding of [3H]ouabain to (Na+-K+)ATPase and inhibited (Na+-K+)ATPase activity. The multiple inhibition technique was used to demonstrate that canrenone is a partial inhibitor of (Na+-K+)ATPase, mutually exclusive with respect to ouabain. Comparative studies of the effects of ouabain and canrenone on K-dependent p-nitrophenylphosphatase activity and K activation of (Na+-K+)ATPase confirmed that ouabain and canrenone interacted with the same receptor site. The finding that canrenone is a partial agonist may explain the results of previous in vivo studies showing that spironolactone and the allied drug potassium canrenoate have a positive inotropic action or an antagonistic effect against digitalis toxicity in animals.

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